What immune support is suitable for a patient with long Covid and Multiple Myeloma (MM) with a history of potentially misdiagnosed tumor-induced osteomalacia?

Immune Support for Long COVID Patient with Multiple Myeloma

For this patient with long COVID and multiple myeloma (MGUS), prioritize COVID-19 vaccination per CDC guidelines, annual influenza vaccination, pneumococcal vaccination, and varicella zoster vaccination, while avoiding live vaccines entirely. 1

Vaccination Strategy

Core Vaccinations Required

• COVID-19 vaccination following CDC guidelines is essential for patients with hematological malignancies like multiple myeloma, as they face significantly higher mortality risk from COVID-19 infection 2

• Annual influenza vaccination is strongly recommended, preferably using a two-dose series at least one month apart of high-dose influenza vaccine to increase likelihood of seroprotection in immunocompromised patients 2

• Pneumococcal vaccination should be administered given the seven-fold increased susceptibility to bacterial infections in MM patients 2

• Varicella zoster vaccination is recommended, though patients should continue anti-viral prophylaxis as there are no clear data on stopping prophylaxis following vaccination 2

Critical Vaccination Precautions

• Live attenuated vaccines are absolutely contraindicated in multiple myeloma patients, with the sole exception being patients who underwent autologous stem cell transplant more than 24 months prior with complete immune reconstitution 2, 1

• Inactivated vaccines are preferred and appear particularly safe when myasthenia gravis (if present) is stable/well-controlled 1

• Timing considerations: If the patient is on high-dose or long-term corticosteroids, consider delaying vaccination until 4-6 weeks after treatment if clinically feasible 1

Expected Vaccine Response in MM Patients

Anticipated Immunogenicity

• Multiple myeloma patients show variable vaccine responses (45-95% antibody response after 2 doses of mRNA COVID-19 vaccine), but consistently lower antibody titers than healthy controls 2

• Factors impairing response include older age, number of previous treatment lines, low lymphocyte count, and specific treatments like daratumumab-based regimens 2

• Important caveat: Immunity following vaccination is not guaranteed in MM patients due to immune-regulating treatments, though vaccinations may induce protective T-cell responses even without antibody responses 2

Infection Prophylaxis Considerations

Anti-Viral Prophylaxis

• Herpes virus prophylaxis with acyclovir or valacyclovir should be considered, particularly if the patient has received anti-CD38 antibodies or other immunosuppressive MM treatments 2

• Pneumocystis jirovecii prophylaxis with trimethoprim-sulfamethoxazole, dapsone, or atovaquone is recommended for patients on intensive MM therapy, though this may not apply if MGUS diagnosis is confirmed 2

Hepatitis B Screening

• Screen for hepatitis B with core antibodies and surface antigens prior to any intensification of treatment, with prophylaxis or monitoring based on results 2

Household and Healthcare Provider Vaccination

• Close contacts should receive seasonal vaccines including influenza and COVID-19 to create a protective environment around this immunocompromised patient 2, 1

• Healthcare providers caring for this patient should be fully immunized and receive seasonal vaccines 2, 1

Regarding the Tumor-Induced Osteomalacia Question

Diagnostic Clarification Needed

• Elevated FGF23 with improving vitamin D suggests the initial tumor-induced osteomalacia diagnosis may have been correct, as TIO is characterized by elevated or inappropriately normal FGF23 levels with low to low-normal 1,25(OH)2D 3, 4

• TIO is frequently misdiagnosed (>95% initial misdiagnosis rate) and tumors are typically small, slow-growing, and difficult to locate 3

• If TIO is confirmed, complete surgical excision is curative and would eliminate need for ongoing phosphate supplementation 5, 3

• Functional imaging with 68Ga DOTA-based PET/CT has better sensitivity for tumor localization if surgical cure is being considered 3

Key Clinical Pitfalls to Avoid

• Never administer live vaccines to this patient given the MM/MGUS diagnosis - this includes live attenuated influenza vaccine (LAIV) 2, 1

• Do not assume vaccine protection - consider checking antibody titers 3-5 weeks after vaccination to assess response, particularly for COVID-19 2

• Do not delay urgent vaccinations for minor illness, but ensure myasthenia gravis (if present) is stable before administering vaccines 1

• Monitor for COVID-19 breakthrough infections closely, as MM patients remain at high risk despite vaccination and may require early treatment with antivirals or monoclonal antibodies 2